title: Minimal killing unit of the mitochondrial targeting domain of Noxa.
abstract: Noxa is a key player in p53-induced cell death via mitochondrial dysfunction, and the mitochondrial-targeting domain (MTD) of Noxa is responsible for the translocation of Noxa to mitochondria and for the induction of necrotic cell death. The purpose of this study was to define the minimal killing unit of MTD in vitro and in vivo. It was found that the peptides R8:MTD(10), R8:MTD(9), and R8:MTD(8) can kill various human tumor cells (HCT116, HeLa, MCF-7, BJAB), but that R8:MTD(7) abolishes the killing activity of MTD mainly because of the loss of mitochondrial targeting activity. We find it interesting that R8:MTD(8) was found to kill tumor cells but showed a limited killing activity on normal peritoneal macrophages. Furthermore, R8:MTD(10), R8:MTD(9), and R8:MTD(8) limitedly suppressed tumor growth when injected i.v. into BalB/C mice bearing CT26 cell-derived tumors. These results indicate that MTD(8) is the minimal killing unit of MTD.
authors.affiliation: Department of Biochemistry and Molecular Biology, Chosun University School of Medicine, 309 Pilmoondaero, Gwang-Ju, 501-759, Korea.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Ji Hye
authors.initials: JH
authors.lastname: Han
authors.forename: Ae-Ran
authors.initials: AR
authors.lastname: Moon
authors.forename: Jung Hee
authors.initials: JH
authors.lastname: Park
authors.forename: Jeong Hwan
authors.initials: JH
authors.lastname: Chang
authors.forename: Jeehyeon
authors.initials: J
authors.lastname: Bae
authors.forename: Tae-Hyoung
authors.initials: TH
authors.lastname: Kim
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009368:Neoplasm Transplantation; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D021382:Protein Sorting Signals; D017434:Protein Structure, Tertiary; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; C498702:PMAIP1 protein, human; D010446:Peptide Fragments; D021382:Protein Sorting Signals; D019253:Proto-Oncogene Proteins c-bcl-2
keywords: Noxa; anti-cancer; deleted MTD peptide; tumor suppression